IDH3A
| IDH3A | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 15: 78.13 – 78.17 Mb | Chr 9: 54.49 – 54.51 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (IDH3α) is an enzyme that in humans is encoded by the IDH3A gene.[5][6]
heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the alpha subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. [provided by RefSeq, Jul 2008][6]
Structure
IDH3 is one of three isocitrate dehydrogenase isozymes, the other two being
substrate isocitrate, all three subunits participate in the catalytic reaction.[10][11] Moreover, studies of the enzyme in pig heart reveal that the αβ and αγ dimers constitute two binding sites for each of its ligands, including isocitrate, Mn2+, and NAD, in one IDH3 tetramer.[9][10]
Function
As an isocitrate dehydrogenase, IDH3 catalyzes the irreversible oxidative decarboxylation of isocitrate to yield
Clinical significance
IDH3α expression has been linked to
HIF-1. HIF-1 is largely known for shifting glucose metabolism from oxidative phosphorylation to aerobic glycolysis in cancer cells (the Warburg effect). Moreover, IDH3α activity leads to angiogenesis and metabolic reprogramming to provide the necessary nutrients for continuous cell growth. Meanwhile, silencing IDH3α is observed to obstruct tumor growth. Thus, IDH3α may prove to be a promising therapeutic target in treating cancer.[8]
IDH3α is also implicated in
psychiatric disorders. In particular, IDH3α expression in the cerebellum is observed to be significantly lower for bipolar disorder, major depressive disorder, and schizophrenia. The abnormal IDH3α levels may disrupt mitochondrial function and contribute to the pathogenesis of these disorders.[13]
Mutations in this gene have been associated with autosomal recessive retinitis pigmentosa.[14]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000166411 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032279 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 8833160.
- ^ a b "Entrez Gene: IDH3A isocitrate dehydrogenase 3 (NAD+) alpha".
- PMID 25678837.
- ^ PMID 25531325.
- ^ PMID 17432878.
- ^ PMID 16737955.
- ^ PMID 14555658.
- PMID 20435888.
- ^ PMID 26782057.
- S2CID 128362107.
Further reading
- Anderson NL, Anderson NG (November 2002). "The human plasma proteome: history, character, and diagnostic prospects". Molecular & Cellular Proteomics. 1 (11): 845–67. PMID 12488461.
- Kim YO, Oh IU, Park HS, Jeng J, Song BJ, Huh TL (May 1995). "Characterization of a cDNA clone for human NAD(+)-specific isocitrate dehydrogenase alpha-subunit and structural comparison with its isoenzymes from different species". The Biochemical Journal. 308 (Pt 1): 63–8. PMID 7755589.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Kim YO, Koh HJ, Kim SH, Jo SH, Huh JW, Jeong KS, Lee IJ, Song BJ, Huh TL (December 1999). "Identification and functional characterization of a novel, tissue-specific NAD(+)-dependent isocitrate dehydrogenase beta subunit isoform". The Journal of Biological Chemistry. 274 (52): 36866–75. PMID 10601238.
- Weiss C, Zeng Y, Huang J, Sobocka MB, Rushbrook JI (February 2000). "Bovine NAD+-dependent isocitrate dehydrogenase: alternative splicing and tissue-dependent expression of subunit 1". Biochemistry. 39 (7): 1807–16. PMID 10677231.
- Adkins JN, Varnum SM, Auberry KJ, Moore RJ, Angell NH, Smith RD, Springer DL, Pounds JG (December 2002). "Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry". Molecular & Cellular Proteomics. 1 (12): 947–55. PMID 12543931.
- Soundar S, Park JH, Huh TL, Colman RF (December 2003). "Evaluation by mutagenesis of the importance of 3 arginines in alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase". The Journal of Biological Chemistry. 278 (52): 52146–53. PMID 14555658.
- Guo D, Han J, Adam BL, Colburn NH, Wang MH, Dong Z, Eizirik DL, She JX, Wang CY (December 2005). "Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress". Biochemical and Biophysical Research Communications. 337 (4): 1308–18. PMID 16236267.
- Soundar S, O'hagan M, Fomulu KS, Colman RF (July 2006). "Identification of Mn2+-binding aspartates from alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase". The Journal of Biological Chemistry. 281 (30): 21073–81. PMID 16737955.
- Bzymek KP, Colman RF (May 2007). "Role of alpha-Asp181, beta-Asp192, and gamma-Asp190 in the distinctive subunits of human NAD-specific isocitrate dehydrogenase". Biochemistry. 46 (18): 5391–7. PMID 17432878.
